EUCAST Expert Rules in Antimicrobial Susceptibility Testing - eibne.gr

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and Gram-positive organisms, respectively. Topoisomerase mutations in gyrA and parC genes and reduction in target access, including porin modification and efflux systems, are the classical chromosomally encoded mechanisms affecting these compounds. Topoisomerase mutations can confer high level resistance, mainly due to stepwise selection of several mutations in the same or different topoisomerase [87]. Plasmid-mediated quinolone resistance mechanisms have emerged in Gram-negative bacilli during the last decades, and are now frequently observed in many parts of the world [88]. All of them demonstrate low expression and do not always affect all fluoroquinolone agents. Target protection mechanisms due to the Qnr proteins were the first described plasmid mediated resistance mechanisms [89]. Several families of these proteins have now been described, mainly in Enterobacteriaceae. In addition, enzymatic modification due to a mutated aminoglycoside modifying enzyme and also affecting only certain fluoroquinolones has been identified in these organisms. This enzyme [AAC(6’)-Ib-cr] affects C7-piperazinyl substituted fluoroquinolones, ciprofloxacin and norfloxacin, but not levofloxacin [90]. More recently, two plasmid-mediated efflux- based mechanisms involving the QepA and OqxAB pumps related to major facilitator superfamily (MFS) transporters were described. In this case the resistance is low-level and phenotypic detection is extremely difficult [91,92]. In general, older quinolones have lower activity than more recently developed agents. This is more obvious with Gram-negative organisms and is particularly evident in Enterobacteriaceae. However, particularly with resistance due to mutations in topoisomerases, decreased susceptibility to one fluoroquinolone is reflected in reduced susceptibility to other fluoroquinolones (class resistance). With these isolates, the concomitant presence of different mutations increases the level of fluoroquinolone resistance. Nevertheless, Qnr proteins, efflux and enzymatic modification resistance mechanisms may not confer resistance to all fluoroquinolones. Such low-level resistance mechanisms are difficult to detect but they indicate the potential for selection of higher- level resistance mechanisms.
When reading antibiograms with quinolones, resistance to the most active fluoroquinolone in vitro indicates resistance to all fluoroquinolones in both Gram-negative and Gram-positive organisms [93-95]. An exception to this rule in Gram-negatives is the potential production of the AAC(6’)-Ib-cr enzyme that affects ciprofloxacin but not levofloxacin EUCAST interpretive rules for fluoroquinolones (rules 13.2, 13.4, 13.5, 13.6, and 13.8) all take this approach, supported by different levels of evidence (grades B or C). In some organisms (i.e. Enterobacteriaceae and H. influenzae), nalidixic acid can be used as a predictor of resistance mechanisms affecting fluoroquinolones [96-98]. However, in Enterobacteriaceae this compound does not detect qnr- or other plasmid-mediated quinolone resistance, which is increasingly recognized all over the world. For this reason, in version 2 of the expert rules modification of fluoroquinolone susceptibility results on the basis of ciprofloxacin MIC values is recommended for Salmonella spp. as there is clear clinical evidence for ciprofloxacin to indicate a poor response in systemic infections caused by Salmonella spp. with low-level quinolone resistance (MIC>0.064 mg/L) (rule 13.6). The available data relate mainly to S. Typhi but there are also case reports of poor response with other Salmonella species [96,98,99]. On the contrary, rule 13.6 does not apply to other Enterobacteriaceae as there is a lack of such clear clinical evidence and generalization cannot be recommended. Nevertheless, laboratories might alert clinicians to the possible of emergence of high level resistance to fluoroquinolones in Enterobacteriaceae with low level resistance to these compounds when using fluoroquinolones. In staphylococci and viridans group streptococci, resistance to the less active, but not to the more active fluoroquinolones, indicates that a first step mutation may be present. In this case, a warning should be added to the susceptibility testing report alerting clinicians to the potential for selection of a higher-level resistance mechanism involving different mutations (rules 13.1 and 13.3). Inference of specific fluoroquinolone resistance mechanisms can be difficult in multidrug- resistant organisms as they may have superimposed mechanisms affecting these compounds (low- and/or high-level resistance). Moreover, with any of the new plasmid mediated resistance
Page 1 and 2: Received Date : 31-Aug-2011 Revised
Page 3 and 4: Introduction Antimicrobial suscepti
Page 5 and 6: the rule. EUCAST interpretive rules
Page 7 and 8: For this objective, different rules
Page 9 and 10: Enterococci. All enterococci are co
Page 11 and 12: low-level expression, such as with
Page 13 and 14: cross-resistance between erythromyc
Page 15: Despite this apparent complexity, s
Page 19 and 20: Transparency declarations Nothing t
Page 21 and 22: 29. Hawser SP, Badal RE, Bouchillon
Page 23 and 24: 51. Morikawa Y, Kitazato M, Mitsuya
Page 25 and 26: 80. Martin P, Jullien E, Courvalin
Page 27 and 28: 106. Jarlier V, Soussy CJ, Chanal M
Page 29 and 30: Table 1. Intrinsic resistance in En
Page 31 and 32: Table 3. Intrinsic resistance in Gr
Page 33 and 34: Table 5. Exceptional phenotypes of
Page 35 and 36: Table 7. Exceptional phenotypes of
Page 37 and 38: pneumoniae diffusion) 8.5 Viridans
Page 39 and 40: coli) Does not apply to inhibitor c
Page 41 and 42: 10.4 Neisseria gonorrhoeae Benzylpe
Page 43 and 44: 11.3 Streptococcus spp. Erythromyci
Page 45 and 46: Table 12. Interpretive rules for am
Page 47 and 48: Enterobacteriaceae gentamicin amika
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13.6 Salmonella spp. Ciprofloxacin
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